title: Fucans, but not fucomannoglucuronans, determine the biological activities of sulfated polysaccharides from Laminaria saccharina brown seaweed.
abstract: Sulfated polysaccharides from Laminaria saccharina (new name: Saccharina latissima) brown seaweed show promising activity for the treatment of inflammation, thrombosis, and cancer; yet the molecular mechanisms underlying these properties remain poorly understood. The aim of this work was to characterize, using in vitro and in vivo strategies, the anti-inflammatory, anti-coagulant, anti-angiogenic, and anti-tumor activities of two main sulfated polysaccharide fractions obtained from L. saccharina: a) L.s.-1.0 fraction mainly consisting of O-sulfated mannoglucuronofucans and b) L.s.-1.25 fraction mainly composed of sulfated fucans. Both fractions inhibited leukocyte recruitment in a model of inflammation in rats, although L.s.-1.25 appeared to be more active than L.s.-1.0. Also, these fractions inhibited neutrophil adhesion to platelets under flow. Only fraction L.s.-1.25, but not L.s.-1.0, displayed anticoagulant activity as measured by the activated partial thromboplastin time. Investigation of these fractions in angiogenesis settings revealed that only L.s.-1.25 strongly inhibited fetal bovine serum (FBS) induced in vitro tubulogenesis. This effect correlated with a reduction in plasminogen activator inhibitor-1 (PAI-1) levels in L.s.-1.25-treated endothelial cells. Furthermore, only parent sulfated polysaccharides from L. saccharina (L.s.-P) and its fraction L.s.-1.25 were powerful inhibitors of basic fibroblast growth factor (bFGF) induced pathways. Consistently, the L.s.-1.25 fraction as well as L.s.-P successfully interfered with fibroblast binding to human bFGF. The incorporation of L.s.-P or L.s.-1.25, but not L.s.-1.0 into Matrigel plugs containing melanoma cells induced a significant reduction in hemoglobin content as well in the frequency of tumor-associated blood vessels. Moreover, i.p. administrations of L.s.-1.25, as well as L.s.-P, but not L.s.-1.0, resulted in a significant reduction of tumor growth when inoculated into syngeneic mice. Finally, L.s.-1.25 markedly inhibited breast cancer cell adhesion to human platelet-coated surfaces. Thus, sulfated fucans are mainly responsible for the anti-inflammatory, anticoagulant, antiangiogenic, and antitumor activities of sulfated polysaccharides from L. saccharina brown seaweed.
authors.affiliation: Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas y Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
authors.forename: Diego O
authors.initials: DO
authors.lastname: Croci
authors.forename: Albana
authors.initials: A
authors.lastname: Cumashi
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Ushakova
authors.forename: Marina E
authors.initials: ME
authors.lastname: Preobrazhenskaya
authors.forename: Antonio
authors.initials: A
authors.lastname: Piccoli
authors.forename: Licia
authors.initials: L
authors.lastname: Totani
authors.forename: Nadezhda E
authors.initials: NE
authors.lastname: Ustyuzhanina
authors.forename: Maria I
authors.initials: MI
authors.lastname: Bilan
authors.forename: Anatolii I
authors.initials: AI
authors.lastname: Usov
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Grachev
authors.forename: Galina E
authors.initials: GE
authors.lastname: Morozevich
authors.forename: Albert E
authors.initials: AE
authors.lastname: Berman
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Sanderson
authors.forename: Maeve
authors.initials: M
authors.lastname: Kelly
authors.forename: Patrizia
authors.initials: P
authors.lastname: Di Gregorio
authors.forename: Cosmo
authors.initials: C
authors.lastname: Rossi
authors.forename: Nicola
authors.initials: N
authors.lastname: Tinari
authors.forename: Stefano
authors.initials: S
authors.lastname: Iacobelli
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
authors.forename: Nikolay E
authors.initials: NE
authors.lastname: Nifantiev
mesh_terms: D020533:Angiogenesis Inhibitors / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D000925:Anticoagulants / Q000378:metabolism / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D005643:Fucose / Q000737:chemistry / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D007795:Laminaria / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D000459:Phaeophyceae / Q000737:chemistry / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012624:Seaweed / Q000737:chemistry / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D001688:Biological Products; D011134:Polysaccharides; D005643:Fucose; C007789:fucoidan